tbuckley/cabot-search huggingface dataset:
Epidemiology, clinical features and outcomes of ganglioneuroblastoma: An analysis of the National Cancer Database.
Authors: Bridgett Nelson, Peter T. Silberstein, Gregory Cichon
Journal: Journal of Clinical Oncology (2022)

e22013 Background: Ganglioneuroblastoma (GNB) is a rare tumor of the sympathetic nervous system composed of both immature neuroblasts and mature ganglion cells. It has an intermediate malignant potential that lies between a low grade ganglioneuroma and a high-grade neuroblastoma and has the capability to transform into a neuroblastoma. While more information is known regarding pediatric neuroblastoma, little is known regarding the epidemiology and clinical features of GNB. To our knowledge, this is the first analysis of ganglioneuroblastoma using the National Cancer Database (NCDB) and potentially the largest and most comprehensive studies of this subtype of tumor to date. Methods: Using the National Cancer Database (NCDB), 273 patients diagnosed with ganglioneuroblastoma (ICD-0 9490/3) from 2004-2018 were identified. Kaplan-Meir analysis was used to estimate survival and log-rank tests were used to compare survival between stage groups. Results: The median age of diagnosis for patients with ganglioneuroblastoma was found to be 4 years. Girls were affected more commonly than boys, with a male to female ratio of 1.6/1. A majority of patients were white (77.7%) and African American (13.6%), followed by minor representations from multiple other races. The most common primary site of ganglioneuroblastoma was the thorax (40.5%), followed by the abdomen (35.7%). A minority of patients (14%) had distant metastases at diagnosis. At the time of disease presentation, 56% of patients were classified as stage I, 9.2% as stage II, 18.4% as stage III and 16.3% as stage IV. Stages I, II, and III conferred an excellent prognosis with a 99.2% survival rate as compared to patients with stage IV disease who had a survival rate of 65.2% (p &lt; 0.001). Nearly all patients underwent surgery of the primary site, with the most common approach being local excision. Around one quarter of patients received chemotherapy while very few patients required radiation or immunotherapy. Conclusions: A number of unique findings help to distinguish ganglioneuroblastoma from the more common variant neuroblastoma. GNB seems to affect slightly older children (median age of 4 years) compared to a median age of 22 months in neuroblastoma. Interestingly, GNB was found to occur significantly more frequently in girls. On the contrary, neuroblastoma has been reported to be slightly more common in males than females. Additionally, the majority of ganglioneuroblastomas arise in the thorax. This is in comparison to neuroblastomas, of which the large majority arise in the abdomen, specifically in the adrenal glands. Stage IV GNB carries a significantly worse prognosis than stages I-III, with a survival rate of 62.5% which is similar to stage IV neuroblastoma.
Prevention and detection of iatrogenic ureteral injury during abdominal or pelvic surgery: A systematic review and meta-analysis
Authors: T. Yanagiswawa, K. Mori, T. Kawada, H. Mostafaei, F. Quhal, E. Laukhtina, P. Rajwa, R. Sari Motlagh, K. Frederik, M. Pallauf, B. Pradere, J. Miki, T. Kimura, S. Egawa, S.F. Shariat
Journal: European Urology (2022)
The association between human gut microbiota and prostate enlargement
Authors: K. Takezawa, K. Fujita, M. Matsushita, D. Motooka, K. Hatano, E. Banno, N. Shimizu, T. Takao, S. Takada, K. Okada, S. Fukuhara, H. Kiuchi, H. Uemura, S. Nakamura, Y. Kojima, N. Nonomura
Journal: European Urology (2022)
A novel predictor for the use of concurrent chemotherapy in early-stage cervical cancer with intermediate-risk factors.
Authors: Guangyu Zhang, Chunli Fu, Changdong Ma, Youzhong Zhang, Li Miao, Cong Wang
Journal: Journal of Clinical Oncology (2022)

e17521 Background: For early-stage cervical cancer patients experiencing radical surgery, postoperative radiotherapy was recommended for patients with a combination of intermediate-risk factors. However, there was no consensus on whether to administer concurrent chemotherapy. The aim of the study was to confirm the clinical value of the controlling nutritional status (COUNT) score in guiding the use of concurrent chemotherapy in patients with early-stage cervical cancers during postoperative radiotherapy. Methods: A total of 945 patients with FIGO stage IB-IIA (2009) cervical cancer were retrospectively analyzed in the study from 2009 to 2018. There were 503 patents receiving concurrent chemoradiotherapy, while another 442 patents undergone radiotherapy lonely. Radiotherapy was performed by conformal radiotherapy or intensity-modulated radiotherapy. The concurrent chemotherapy regimen included either cisplatin or paclitaxel. Pre-treatment CONUT score were calculated within 1 weeks before curative resection. Low CONUT group and high CONUT group were defined based on the cutoff value of CONUT score which was determined by the receiver operating characteristic analysis. Kaplan-Meier survival analysis was performed to compare disease-free survival (DFS) and cancer-specific survival (CSS) rates between different group. A Cox proportional hazards regression test was used to conduct multivariate analyses of DFS, local recurrence-free survival and distant metastasis-free survival (DMFS). Results: The median follow-up was 54.6 months (range: 4.8-147.5 months). The optimal cutoff value of CONUT was 3 in the study. For the patients included in the high CONUT group (≥3), the addition of concurrent chemotherapy significantly improved treatment outcomes, and had better 5-year DFS (90.37% vs 70.69%, P &lt; 0.001) and CSS (95.02% vs 78.74%, P = 0.005) than those without it. Meanwhile, the patients with concurrent chemotherapy had less rate of distant metastasis (6.5% vs 28.1%, P &lt; 0.001). For the patients included in low CONUT group (&lt; 3), there was no difference in prognosis between patients receiving concurrent chemotherapy and not receiving. In the high CONUT group, the multivariate analysis showed that concurrent chemotherapy was detected to be a factor significantly associated with DFS (HR 3.077; 95% CI: 1.295-6.679, P = 0.011) and DMFS (HR 3.435; 95% CI: 1.506-7.014, P = 0.006). Conclusions: Pre-treatment CONUT score may be a predictive factor for the use of concurrent chemotherapy in early-stage cervical cancer patients with intermediate-risk factors during postoperative radiotherapy, and it can be helpful to determine the adjuvant treatment scheme.
A phase 2, randomized, open-label, multicenter study of sintilimab and anlotinib in combination with gemcitabine plus cisplatin (GemCis) as first-line therapy in patients (pts) with advanced biliary tract cancer (BTC): SAGC.
Authors: Li Jingjing, Xu Qi, Qing Wei, Zhe Han, Luo Cong, Fabiao Zhang, Jieer Ying
Journal: Journal of Clinical Oncology (2022)

4100 Background: BTC has a higher incidence in China rather than worldwide, with extremely poor prognosis, and the efficacy of standard first-line therapy (GemCis) is rather limited. TOPAZ-1 study suggested immunotherapy + GemCis as first line in advanced BTC significantly improved OS and PFS vs placebo + GemCis with manageable safety, but the median OS was just 12.8 months. SAGC is the first randomized controlled phase 2 trial to evaluate first-line immunotherapy + antiangiogenic targeted drug + GemCis in advanced BTC. Methods: In this randomized controlled study, pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomized 1:1 to receive sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) in combination with GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) or GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles until disease progression or unacceptable toxicity. The primary objective was to assess the 1-year overall survival (OS). Secondary endpoints included OS, progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff for this interim analysis (11 November, 2021), 48 pts were randomized to sintilimab + anlotinib + GemCis (n=26) or GemCis (n=22). The primary objective was not meet: the 1-year OS was 52.5% with sintilimab + anlotinib + GemCis and 36.3% with GemCis (p=0.437), but there was a trend of nominal OS benefit in patients treated with sintilimab + anlotinib + GemCis. PFS was significantly improved with sintilimab + anlotinib + GemCis vs GemCis (6.4m vs 5m; p=0.014). ORR was 37.5% with sintilimab + anlotinib + GemCis and 26.7% with GemCis. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 69.2% of pts receiving sintilimab + anlotinib + GemCis and38.7% of pts receiving GemCis. TRAEs led to discontinuation of any study medication in 7.7% of pts receiving sintilimab + anlotinib + GemCis and 9.1% of pts receiving GemCis. Conclusions: In pts with advanced BTC, sintilimab + anlotinib + GemCis could improve OS and PFS vs GemCis with manageable safety, indicating sintilimab + anlotinib + GemCis may be a new first-line standard of care regimen. Research Sponsor: Innoventbio Biologics, Inc, Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Clinical trial information: NCT04300959.
Avoiding Toxicity With Lung Radiation Therapy: An IASLC Perspective
Authors: Nicholas W. Bucknell, José Belderbos, David A. Palma, Puneeth Iyengar, Pamela Samson, Kevin Chua, Daniel Gomez, Fiona McDonald, Alexander V. Louie, Corinne Faivre-Finn, Gerard G. Hanna, Shankar Siva
Journal: Journal of Thoracic Oncology (2022)
Changes in Circulating miR-375-3p and Improvements in Visceral and Hepatic Fat Contents in Response to Lifestyle Interventions: The CENTRAL Trial
Authors: Yoriko Heianza, Knut Krohn, Anat Yaskolka Meir, Xuan Wang, Stefanie Ziesche, Uta Ceglarek, Matthias Blüher, Maria Keller, Peter Kovacs, Iris Shai, Lu Qi
Journal: Diabetes Care (2022)

To investigate whether changes in circulating levels of pancreatic islet-related miRNA-375 (miR-375) are related to improved visceral and intrahepatic fat accumulation.This study included adults with abdominal obesity from an 18-month weight loss lifestyle intervention trial. Circulating miR-375-3p was measured at baseline and 18 months. MRI was performed (n = 139) to assess 18-month changes in abdominal and intrahepatic fat depots.Circulating miR-375-3p was related to fasting insulin and insulin resistance in participants with prediabetes. After the interventions, there was a significant increase of miR-375-3p (P < 0.001). Greater increase in miR-375-3p was associated with greater reductions of visceral (P = 0.024) and deep subcutaneous (P < 0.001) adipose tissues and intrahepatic fat content (P = 0.012).Increases in circulating miR-375-3p were associated with visceral and intrahepatic fat reduction. Changes in circulating pancreatic islet-related miR-375-3p may be linked to improved diabetogenic fat depots during weight loss lifestyle interventions.
EPEN-08. Single-cell transcriptome analysis defines a tumor-supportive microenvironment and tumor-stroma crosstalk in pediatric ependymoma and medulloblastoma.
Authors: Aniello Federico, Konstantin Okonechnikov, Enrique Blanco Carmona, Julie A S Lammers, Mariette E G Kranendonk, Johannes Gojo, Bernhard Englinger, Li Jiang, Stefan Nierkens, Friso G J Calkoen, Jasper van der Lugt, Mariella G Filbin, Natalie Jäger, Stefan M Pfister, Marcel Kool
Journal: Neuro-Oncology (2022)

Abstract Brain tumors are the leading cause of disease-related death in childhood and strong efforts are required to develop innovative and efficient therapeutic strategies for patients with high-risk disease. Key critical factor of pediatric brain tumors is their molecular heterogeneity; one of the aspects that contributes to such heterogeneity is the intrinsic capacity of the tumor cells to organize, shape and exploit the surrounding brain tumor microenvironment (TME) to sustain tumor growth and malignant progression. TME was proved to play a crucial role in several malignancies, but in pediatric brain malignancies this has not been fully elucidated yet. Here, we aimed at characterizing the TME cell populations and their contributions in ependymoma and medulloblastoma, two of the most common pediatric brain tumor entities. Single-cell transcriptome analysis (n=65 ependymomas; n=39 medulloblastomas) of publicly available tumor datasets, as well as newly generated data of primary tumors and matching patient-derived tumor xenografts (PDX), showed an extensive heterogeneity of TME cell types with distinctive expression signatures. Amongst the identified TME populations, analysis revealed pro-inflammatory and proliferating myeloid cells, tumor-infiltrating lymphocytes, active regulatory T cells and vascular progenitor cells. Comparative analysis between primary and PDX tumors showed that tumor cells stimulated the host microenvironment, which in turn exhibited tumor-associated stromal signatures. Applying a deconvolution method, using our single cell data as reference, on a bulk tumor cohort including PFA ependymomas with different degree of immune infiltration, we observed an enrichment of polarized macrophages and microglia cells in tumor with high infiltration. Next, we identified TME markers involved in tumor-supportive functions, such as immune suppression (TIGIT, FOXP3, BCL2, CD19, ICAM2), pro-inflammatory stimuli (CCL3, CCL4, IL1B, GPNMB), extracellular matrix remodeling (COL4A1) and angiogenic processes (ANGPT2). TME markers with emerging role in ependymoma and medulloblastoma can be considered as possible targets for tailored and more effective anti-tumor therapeutic strategies.
Evaluation of a pharmacist-led video consultation to identify drug interactions among patients initiating oral anticancer drugs.
Authors: Morgan RL Lichtenstein, Khilna Patel, Peter Campbell, Michelle K. Nguyen, Erik Harden, John Spivack, Nicole Collins, Khadija Faheem, Melissa Parsons Beauchemin, Katherine D. Crew, Melissa Kate Accordino, Meghna S. Trivedi, Elena B. Elkin, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2022)

1592 Background: The past decade has seen a dramatic increase in the number of oral anti-cancer drug (OACD) approvals in the United States. Though polypharmacy and drug-drug interactions (DDIs) likely contribute to OACD toxicity, the prevalence of these features in patients on OACDs remains largely unknown. We aimed to evaluate a one-time 30-minute pharmacist-led video consultation among metastatic cancer patients initiating OACDs to identify medication list inaccuracies as well as the prevalence, characteristics, and severity of OACD-related potential DDIs. Methods: We conducted a single-arm, prospective telehealth intervention study among 29 patients initiating OACDs to evaluate a one-time 30-minute pharmacist-led video consultation. The video visits focused on identifying and discussing polypharmacy and potential DDIs, and pharmacists then communicated recommendations to each patient's oncologist. We estimated the prevalence, characteristics (QTc prolongation, absorption interactions, etc.), and severity of OACD-related potential DDIs. Lexicomp and Micromedex were used to assess potential DDIs and measure severity on a standardized scale (A – D, X). In addition, we assessed the prevalence of medication list inaccuracies, polypharmacy, and patient satisfaction. Results: Twenty-five patients completed the intervention (86% completion rate) of whom 40% were 75 years of age or older and 60% were men. The majority were white (68%) and non-Hispanic (76%). Sixteen patients (68%) had a solid tumor diagnosis. Nearly half (48%) were insured by Medicare. The median number of medications per patient was 9 with a range of 4 – 21, and 96% of patients had at least 5 prescriptions listed. The median number of medication list errors was 2 with a range of 0 – 16, with at least 1 error for 76% and more than 1 error for 52% of patients. Pharmacists identified potential OACD-related interactions in 9 cases (40%). These included change in drug absorption or metabolism (7), QTc prolongation (1), hypotension (1), and bleeding (1). Interactions were classified as either category C (8) or D (2), requiring close monitoring or a change in treatment, respectively. All patients expressed a high level of satisfaction with the video visit. Conclusions: Polypharmacy, medication list errors, and potential DDIs are prevalent among patients initiating OACDs despite use of an electronic medical record requiring medication reconciliation. Our study suggests that a one-time remote 30-minute pharmacist-led video consultation can effectively identify and address OACD-related potential DDIs, which may decrease medication complexity and improve adherence in this population.
Analysis of non-sentinel lymph node status on 10-year overall survival among patients with breast cancer and sentinel lymph node metastasis.
Authors: Huizi Lei, Pei Yuan, Binghe Xu, Jianming Ying
Journal: Journal of Clinical Oncology (2022)

e12584 Background: To investigate retrospectively the effect of non-sentinel lymph node status (non-SLN) on 10-year overall survival (OS) and non-SLN metastasis risk factors in patients with breast cancer and sentinel lymph node (SLN) metastasis. Methods: A large population (n = 15510) underwent SLN dissection in Cancer Hospital, Chinese Academy of Medical Sciences from 2011 to 2022. In total, 3033 (19.6%) cases had at least one SLN metastasis, which underwent axillary lymph node (ALN) dissection. The clinicopathological characteristics and their relationship with non-SLN status were analyzed. Among patients from 2011-2012(n = 132), the effect of non-SLN status on 10-year OS and disease-free survival (DFS) with SLN metastasis were also analyzed. Results: In 3033 patients with SLN metastasis, the mean age was (50.42±10.59) years. The average number of SLN metastasis in each patient was 1.75±1.21, the average number of SLN detected was 4.89±2.03 and the average number of ALN removed was 22.36±8.88. The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis ( P&lt; 0.05), but not the age, T stage and histological grade. In 132 patients from 2011-2012, a median follow-up of 9.1 years (interquartile range, 7.3-9.5 years), the non-SLN metastasis occurred in 60 cases (45.5%), DFS 70.8%, OS 85.9%; non-SLN non-metastasis occurred in 72 cases (54.5%), DFS 85.6%, OS 90.4%. There was no significant difference between two groups in DFS(χ² = 0.61, P = 0.43) and OS (χ² = 0.06, P = 0.81). Conclusions: The number of SLN metastasis≥2 and positive lympho-vascular invasion were risk factors of non-SLN metastasis. There were no significant differences between non-SLN metastasis group and non-metastasis group in DFS and OS.
Genomic signatures in young and old Chinese patients with bone and soft tissue tumors.
Authors: Gu Jin, Yangyang Yu, Lele Zhao, Mingzhe Xiao, Chuang Qi
Journal: Journal of Clinical Oncology (2022)

e23516 Background: The tumor onset of bone and soft tissue at young or old age was associated with different clinical features. However, the genomic differences between young and old patients with bone and soft tissue tumors were not well elucidated. Therefore, a comprehensive molecular profile in young and old patients should be defined, which will enhance our understanding of the unique biology of bone and soft tissue tumors and help to improve the treatment options for this population. Methods: Tumor tissue samples from 103 young (age &lt; = 50 years) and 81 old (age &gt; 50 years) patients with bone and soft tissue tumors were enrolled, between 2019 to 2021. Targeted sequencing of 539 cancer-related genes was conducted to characterize the genomic landscape. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations (CNV) and gene fusions were assessed and germline alterations were excluded. Tumor mutation burden (TMB) was calculated by counting all nonsynonymous mutations per megabase of coding sequences. Results: The most common mutant genes in the younger and elderly groups were TP53 (20%), MUC16 (13%), KRT2 (8%) and TP53 (37%), MUC16 (19%), LRP1B (10%), FAT3 (7%), respectively. KRT2 mutations were significantly higher in the younger group (7.8% vs. 1.2%, p = 0.041), while TP53 mutations were more common in the elderly group (20.4% vs. 37%, p = 0.012). MUC4 and FADS6 mutations were only observed in the younger group (5.8% and 4.9%). Mutation of some genes were observed simultaneously in certain patients, for instance, TRIOBP/ KRT2, GATSL3 / KRT2, GATSL3 / SSUH2 in the younger group and P53 / LRP1B, MUC16 / PTEN, MUC16 / FAT2, MUC16 / LRP1B, APC / CARD11 in the elderly group. The most frequently affected pathways in the younger and elderly groups were TP53(23.3% vs 37%), RTK-RAS (16.5% vs. 29.6%), NOTCH (16.5% vs.16%), PIK3 (7.8% vs18.5%), Hippo (8.7% vs. 17.2%), respectively. The tumor mutation burden (TMB) was positively correlated with age (Pearson's r = 0.33, p &lt; 0.001), and the old patients had higher TMB. Up to 97.8% (180/184) evaluated samples were microsatellite stable. Conclusions: These findings revealed different molecular characterization between young and old Chinese patients with bone and soft tissue tumors, which may further provide novel insights for the personalized treatment.
Insights into the biosynthesis of septacidin l-heptosamine moiety unveils a VOC family sugar epimerase
Authors: Meng Chen, Zhengyan Guo, Jinyuan Sun, Wei Tang, Min Wang, Yue Tang, Pengwei Li, Bian Wu, Yihua Chen
Journal: Acta Pharmaceutica Sinica B (2022)

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4′-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 (2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4′-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4′-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 (3). An interesting phenomenon is that the SEP intermediates with 4′-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.
Robotic YV plasty for bladder neck vs. vesico-urethral anastomotic stricture
Authors: L. Freton, V. Graffeille, Z. Khene, J. Hascoet, G. Verhoest, R. Mathieu, Q. Vesval, L. Zhao, K. Bensalah, B. Peyronnet
Journal: European Urology (2022)
Pregnancy outcomes in women with psoriatic arthritis: comment on the article by Remaeus et al
Authors: Áine Gorman, Sonia Sundanum, Louise Moore, Celine O'Brien, Fionnula McAuliffe, Douglas J. Veale
Journal: Arthritis & Rheumatology (2022)

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